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Evaluation of chemopreventive agents for genotoxic activity

Rupa S Doppalapudi1, Edward S Riccio, Linda L Rausch

  • 1SRI International, Biosciences Division, Menlo Park, CA 94025, USA. rupa.doppalapudi@sri.com

Mutation Research
|March 28, 2007
PubMed

Insights

This study evaluated 11 chemopreventive agents for genetic toxicity. Most agents were not mutagenic, but indole 3-carbinol and black tea polyphenols showed weak mutagenicity in bacterial assays.

Area of Science:

  • Toxicology and pharmacology
  • Cancer chemoprevention research

Background:

  • Chemopreventive agents hold promise for inhibiting cancer in high-risk individuals.
  • Comprehensive genetic toxicity evaluation is crucial for assessing the safety of potential chemopreventive agents.

Purpose of the Study:

  • To conduct a thorough genetic toxicity assessment of 11 candidate chemopreventive compounds.
  • To identify agents with potential safety concerns for human use.

Main Methods:

  • Bacterial mutagenesis assay (Salmonella-E. coli).
  • Mammalian cell mutagenesis assay (mouse lymphoma).
  • Chromosome aberration assay (Chinese Hamster Ovary cells).
  • Micronucleus induction assay (mouse bone marrow).

Main Results:

  • Most agents were negative in bacterial and mammalian assays, except for indole 3-carbinol (I3C) and black tea polyphenols (BTP) showing weak mutagenicity.
  • 4'-bromoflavone and SR16157 were positive in the chromosome aberration assay under specific metabolic activation conditions.
  • No agents induced micronuclei in mouse bone marrow, suggesting no in vivo genotoxicity in this assay.

Conclusions:

  • The majority of tested chemopreventive agents demonstrated a lack of significant genotoxic potential.
  • Indole 3-carbinol, black tea polyphenols, 4'-bromoflavone, and SR16157 warrant further investigation regarding their genotoxicity profiles.
  • The absence of micronucleus induction suggests a favorable in vivo safety profile for these agents in this specific assay.

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